Trimetazidine: A metabolic modulator and its role in microvascular dysfunction

Cardiovascular disease remains the leading global cause of mortality, with a significant proportion of patients presenting with myocardial ischemia in the absence of obstructive coronary artery disease (CAD), termed microvascular dysfunction (MVD). MVD is underrecognized and challenging to diagnose due to its subtle clinical presentation and limitations in conventional imaging techniques. This narrative review synthesizes current evidence on MVD pathophysiology, diagnostic approaches, and the emerging role of metabolic modulation in its management, with a focus on trimetazidine. We conducted a structured literature search using databases such as PubMed and Scopus up to April 2025. Search terms included “microvascular dysfunction,” “ischemia without obstructive CAD,” “metabolic modulators,” and “trimetazidine.” Studies were selected based on relevance to MVD diagnosis, pathogenesis, and therapeutic approaches, particularly those evaluating trimetazidine in clinical or experimental settings. Data extraction was performed independently by two reviewers, and key findings were synthesized thematically. MVD involves functional and structural abnormalities of the coronary microcirculation, leading to impaired coronary flow reserve and ischemia. Traditional antianginal therapies often fall short in this setting. Trimetazidine, a metabolic agent that shifts myocardial energy metabolism from fatty acid oxidation to glucose oxidation, offers an ischemia-modifying effect without altering hemodynamics. Evidence from clinical trials suggests that trimetazidine can improve anginal symptoms, enhance exercise tolerance, and positively influence endothelial function. Given its safety and efficacy, trimetazidine may serve as an important adjunct in MVD therapy, especially when conventional agents are inadequate. Further randomized controlled trials and real-world studies are warranted to validate its role in improving long-term cardiovascular outcomes in MVD.